Association of Elevated Amyloid and Tau Positron Emission Tomography Signal With Near-Term Development of Alzheimer Disease Symptoms in Older Adults Without Cognitive Impairment
Authors: Cherie Strikwerda-Brown, Diana A. Hobbs, Julie Gonneaud, Frédéric St-Onge, Alexa Pichet Binette, Hazal Ozlen, Karine Provost, Jean-Paul Soucy, Rachel F. Buckley, Tammie L. S. Benzinger, John C. Morris, Victor L. Villemagne, Vincent Doré, Reisa A. Sperling, Keith A. Johnson, Christopher C. Rowe, Brian A. Gordon, Judes Poirier, John C. S. Breitner, Sylvia Villeneuve, Angela Tam, Anne Labonte, Alexa Pichet Binette, Anne-Marie Faubert, Axel Mathieu, Cecile Madjar, Charles Edouard Carrier, Christian Dansereau, Christina Kazazian, Claude Lepage, Cynthia Picard, David Maillet, Diane Michaud, Doris Couture, Doris Dea, Claudio Cuello, Alan Barkun, Alan Evans, Blandine Courcot, Christine Tardif, Clement Debacker, Clifford Jack, David Fontaine, David Knopman, Gerhard Multhaup, Jamie Near, Jeannie-Marie Leoutsakos, Jean-Robert Maltais, Jason Brandt, Jens Pruessner, John Morris, John Breitner, Judes Poirier, Laksanun Cheewakriengkrai, Lisa-Marie MÃ¼nter, Louis Collins, Mallar Chakravarty, Mark Sager, Marina Dauar-Tedeschi, Mark Eisenberg, Natasha Rajah, Paul Aisen, Paule-Joanne Toussaint, Pedro Rosa-Neto, Pierre Bellec, Penelope Kostopoulos, Pierre Etienne, Pierre Tariot, Pierre Orban, Reisa Sperling, Rick Hoge, Ronald Thomas, Serge Gauthier, Suzanne Craft, Sylvia Villeneuve, Thomas Montine, Vasavan Nair, Veronique Bohbot, Vinod Venugopalan, Vladimir Fonov, Yasser Ituria-Medina, Zaven Khachaturian, Eduard Teigner, Elena Anthal, Elsa Yu, Fabiola Ferdinand, Galina Pogossova, Ginette Mayrand, Guerda Duclair, Guylaine Gagne, Holly Newbold-Fox, Illana Leppert, Isabelle Vallee, Jacob Vogel, Jennifer Tremblay-Mercier, Joanne Frenette, Josee Frappier, Justin Kat, Justin Miron, Karen Wan, Laura Mahar, Leopoldina Carmo, Louise Theroux, Mahsa Dadar, Marianne Dufour, Marie-Elyse Lafaille-Magnan, Melissa Appleby, Melissa Savard, Miranda Tuwaig, Mirela Petkova, Pierre Rioux, Pierre-FranÃ§ois Meyer, Rana El-Khoury, Renee Gordon, Renuka Giles, Samir Das, Seqian Wang, Shirin Tabrizi, Sulantha Mathotaarachchi, Sylvie Dubuc, Tanya Lee, Thomas Beaudry, Valerie Gervais, Veronique Page, Julie Gonneaud, GÃ¼lebru Ayranci, Tharick Pascoal, Rene Desautels, Fatiha Benbouhoud, Eunice Farah Saint-Fort, Sander Verfaillie, Sarah Farzin, Alyssa Salaciak, Stephanie Tullo, Etienne Vachon-Presseau, Leslie-Ann Daoust, Theresa Kobe, Nathan Spreng, Melissa McSweeney, Nathalie Nilsson, Morteza Pishnamazi, Christophe Bedetti, Louise Hudon, Claudia Greco, Marianne Chapleau, Frederic St-Onge, Sophie Boutin, Maiya Geddes, Simon Ducharme, Gabriel Jean, Elisabeth Sylvain, Marie-Josee Ã‰lie, Gloria Leblond-Baccichet, Jean-Paul Soucy, Hazal Ozlen, Julie Bailly, Bery Mohammediyan, Yalin Chen, Jordana Remz, Keith Johnson, Dorene Rentz, Rebecca E. Amariglio, Deborah Blacker, Rachel Buckley, Jasmeer P. Chhatwal, Brad Dickerson, Nancy Donovan, Michelle Farrell, Geoffroy Gagliardi, Jennifer Gatchel, Edmarie Guzman-Velez, Heidi Jacobs, Roos Jutten, Cristina Lois Gomez, Gad Marshall, Kate Oaoo, Enmanuelle Pardilla-Delgado, Julie Price, Prokopis Prokopiou, Yakeel Quiroz, Gretchen Reynolds, Aaron Schultz, Stephanie Schultz, Jorge Sepulcre, Irina Skylar-Scott, Patrizia Vannini, Clara Vila-Castelar, Hyun-Sik Yang, Colin L Masters, Larry Ward, Paul Maruff, Christopher Fowler, Ralph Martins, Stephanie Rainy-Smith, Kevin Taddei, Belinda Brown, Simon Laws, Jurgen Fripp, Pierrick Bourgeat
Journal: JAMA Neurology (2022)

Importance National Institute on Aging–Alzheimer’s Association (NIA-AA) workgroups have proposed biological research criteria intended to identify individuals with preclinical Alzheimer disease (AD). Objective To assess the clinical value of these biological criteria to identify older individuals without cognitive impairment who are at near-term risk of developing symptomatic AD. Design, Setting, and Participants This longitudinal cohort study used data from 4 independent population-based cohorts (PREVENT-AD, HABS, AIBL, and Knight ADRC) collected between 2003 and 2021. Participants were older adults without cognitive impairment with 1 year or more of clinical observation after amyloid β and tau positron emission tomography (PET). Median clinical follow-up after PET ranged from 1.94 to 3.66 years. Exposures Based on binary assessment of global amyloid burden (A) and a composite temporal region of tau PET uptake (T), participants were stratified into 4 groups (A+T+, A+T−, A−T+, A−T−). Presence (+) or absence (−) of neurodegeneration (N) was assessed using temporal cortical thickness. Main Outcomes and Measures Each cohort was analyzed separately. Primary outcome was clinical progression to mild cognitive impairment (MCI), identified by a Clinical Dementia Rating score of 0.5 or greater in Knight ADRC and by consensus committee review in the other cohorts. Clinical raters were blind to imaging, genetic, and fluid biomarker data. A secondary outcome was cognitive decline, based on a slope greater than 1.5 SD below the mean of an independent subsample of individuals without cognitive impairment. Outcomes were compared across the biomarker groups. Results Among 580 participants (PREVENT-AD, 128; HABS, 153; AIBL, 48; Knight ADRC, 251), mean (SD) age ranged from 67 (5) to 76 (6) years across cohorts, with between 55% (137/251) and 74% (95/128) female participants. Across cohorts, 33% to 83% of A+T+ participants progressed to MCI during follow-up (mean progression time, 2-2.72 years), compared with less than 20% of participants in other biomarker groups. Progression further increased to 43% to 100% when restricted to A+T+(N+) individuals. Cox proportional hazard ratios for progression to MCI in the A+T+ group vs other biomarker groups were all 5 or greater. Many A+T+ nonprogressors also showed longitudinal cognitive decline, while cognitive trajectories in other groups remained predominantly stable. Conclusions and Relevance The clinical prognostic value of NIA-AA research criteria was confirmed in 4 independent cohorts, with most A+T+(N+) older individuals without cognitive impairment developing AD symptoms within 2 to 3 years.